Experiments are proposed to study the basic electrophysiology of canine and human colonic smooth muscles. The electrical activity of the colon is complicated and has not been adequately described by extracellular recordings. We have developed placement cross- sectional preparations of the colonic muscularis which allow precise placement of intracellular microelectrodes to characterize the electrical activity at any point through the thickness of the muscle. A complete analysis of colonic waveforms will be performed. Preliminary studies have revealed 2 pacemaker zones: one in the region of the myenteric plexus and another at the extreme submucosal surface of the circular layer. The ionic dependence of these rhythmic potential oscillatins will be investigated. The origin and mechanisms of propagation of electrical events will be determined. Our preliminary data have suggested that the bulk of the circular muscle is a passive syncytium which connects the 2 active, pacemaker regions. Events appear to passively spread through the circular muscle from the pacemakers and summate. It is probably the summation of events that results in excitation-contraction coupling in the proximal colon. We will investigate the regulation of electrical summation. An initial hypothesis is that neural regulation controls the frequency and amplitude of the myogenic electrical activity at the pacemaker sites and controls the cable properties of the "bulk" of the circular muscle to regulate the summation of events. We will also characterize differences in ionic channels in cells from several regions through the thickness of the muscularis to understand the ionic basic for the differences in electrical activity and excitability. An attempt will be made to relate the basic electrophysiological events of the colon to mechanical events and colonic motility.